title: Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA.
abstract: A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.
authors.affiliation: Department of Pharmaceutical Engineering, SunMoon University, Asan, Korea.
authors.forename: N H
authors.initials: NH
authors.lastname: Hoang
authors.forename: N L
authors.initials: NL
authors.lastname: Huong
authors.forename: A
authors.initials: A
authors.lastname: Shrestha
authors.forename: J K
authors.initials: JK
authors.lastname: Sohng
authors.forename: Y J
authors.initials: YJ
authors.lastname: Yoon
authors.forename: J W
authors.initials: JW
authors.lastname: Park
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D025364:Streptogramin A / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D014769:Virginiamycin / Q000378:metabolism
chemical_list: C587192:5,6-dihydrovirginiamycin M1; D000900:Anti-Bacterial Agents; D014769:Virginiamycin; D025364:Streptogramin A
keywords: Streptomyces venezuelae; enhanced anti-MRSA activity; microbial biocatalyst; reduced macrocyclic lactone; streptogramin A antibiotic